Disfungsi Telomer Pada Penyakit Autoimun
Authors
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Endang Purwaningsih
Depaertment of Anatomy, Faculty of Medicine, YARSI University
Keywords:
telomere, immune, rheumatoid arthritis, systemic lupus erythematosusAbstract
Telomer merupakan bagian ujung kromosom yang terdiri atas nukleotida non koding dan berfungsi mencegah terjadinya aberasi kromosom. Pemendekan telomer pada setiap kali siklus replikasi sel berhubungan dengan proses penuaan sel. Proses penuaan akan meningkatkan resiko penyakit autoimun. Faktor genetik dapat memicu hilangnya telomer yang diikuti dengan berkembangnya penyakit autoimun. Beberapa penyakit autoimun seperti rematoid artritis (RA), Systemic Lupus Erythematosus (SLE) atau lupus mengalami disfungsi telomer. Pada penderita SLE telomer sel-sel darahnya mengalami pemendekan bermakna terutama pada usia di bawah 45 tahun, yaitu sebesar 35 – 40 bp pertahun, sedangkan usia di atas 60 tahun, pemendekan telomer kurang bermakna. Tetapi aktifitas telomerase sel-sel darah pada pasien SLE cukup tinggi. Pada penderita rematoid artritis, pemendekan telomer mulai terjadi pada usia 25 – 40 tahun. Pada rematoid artritis HLA –DR+ mengalami pemendekan telomer 26 bp lebih besar pertahun dibandingkan HLA-DR-. Telomer pada penderita rematoid artritis laki-laki lebih pendek daripada penderita perempuan. Reduksi panjang telomer tidak berhubungan dengan lamanya menderita rematoid tetapi dipengaruhi oleh genotip HLA-DRB1. Aktivitas telomerase sel T penderita rematoid rendah sehingga mempercepat apoptosis.
Telomeres are the natural ends of linear chromosomes, consisting of non coding nucleotides and function to prevent chromosome abberation, whereas aging is considered as the effect of telomere shortening due to cell replication. In addition aging will increase the risk of autoimmune diseases. Genetic factor can trigger telomere loss, followed by the development of autoimmune diseases. Dysfuntion of telomeres occurs in some of autoimmune diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). Telomere in blood cells of SLE patient significantly shortened in those under 45 years old, around 35-40 bps per year. However, in patients above 60 years old, no significant different is observed. Regardless the age, telomerase activity in blood cells in SLE patient is quite high. Telomere shortening occurs at the age of 25-40 years in RA patients. In RA patients, telomere in HLA –DR+ is shortened by 26 bp higher than HLA-DR- per year. RA male patients have shorter telomere than the female patients. Reduction of telomere length is not related with the period of rheumatic but affected by HLA-DRB1 genotype. Telomerase activity in T cells of RA patient are in ssufficent and lead to advance apoptosis.
References
Andrews NP, Fujii H, Goronzy JJ, Weyand CM 2010. Telomeres and Immunological Diseasesof Aging. Gerontology 56 : 390-403.
Baratawidjaya, Karnen Garna 2006. Imunologi Dasar. Universitas Indonesia Press.
Branch D, Porter T 2000. Autoimune disease. In: James D, Steer P, Weiner C, Gonik B, editors. High risk pregnancy management option. 2 nd ed. New York: W.B Saunders; p. 853-84.
Costenbander KH, Prescott J, Zee RY, and De Vivo I 2011. Immunosenescence and Rheumatoid : Does Telomere Shortening Predict Impending disease? Autoimmune Rev 10 (9): 569 – 573.
Cunningham F, MacDonald P, Gant N, Leveno K, Gilstrap L, Hankins Gea 2001. Connective tissue disorders. In: Williams Obstetrics. 21 st ed. New York: McGraw Hill. p. 1383-99.
Fujii H, Shao L, Colmegna I, Goronzy JJ, and Weyand 2009. Telomerase insufficiency in Rheumatoid arthritis. PNAS 106 (11): 4360 - 4365.
Greider CW and Blackburn EH 1996. Telomeres, Telomerase and Cancer. Scientific American, p: 92. http://www.genethik.de/telomerase.htm Diakses pada tanggal 5 /10/2010
Hathcock KS 2009. Telomere Biology and Immune System. http:www.discoverymedicine.com/Karen-S-Hathcocok/2009/07/25. Diakses pada tangga 4 Desember 2012.
Hodes RJ, Hatchock KS, Weng NP 2002. Telomere in T and B Cells. Nature Rev Immunology 2 : 699 - 706.
Hohensinner PJ, Goronzy JJ, and Weyang CM 2011. Telomere Dysfunction, Autoimmunity and Aging. Aging and Disease 2 (6): 524 - 537.
Honda M, Mengesha E, Albano S et al 2001. Telomere shorthening and decreased replicative potential, contrasted by continued proliferation of telomerase positive CD8+CD28 (lo) T cells in patients with systemic lupus erythematosus. Clin Immunol 99 : 211 – 221.2001.
Kahlenberg JM and Kaplan MJ 2011. The interplay of Inflammation and CardiovascularDisease in Systemic Lupus Erythematosus . Arthritis Res and Therapy 13 : 203 -213.
Kaszubowska L 2008. Telomere Shortening and Ageing of The Immune System. J of Physiol Pharmacol 59: Suppl 9: 169 – 186.
Katayama Y and Kohriyama K 2001. Telomerase activity in peripheral blood mononuclear cells of Systemic connective tissue diseases. J Rheumatoid 28 : 288- 289.
Kurosaka D, Yasuda J, Yoshida K, Yokoyama T, Ozama Y, Obayashi Y, kingetsu I, Saito S, and Yamada A 2003. Telomerase Activity and Telomere length of Peripheral Blood Mononuclear Cells in SLE patients. Lupus 12 : 591 - 599.
Miller RA 2000. Telomere Diminution as cause of Immune Failure in Old Age.: an unfashionable demurral. BST 28 (2); 241 - 245.
Musai M 2010. Terapi Lupus Eritematosus Sistemik dengan Penghambatan Konstimulasi Sel T. MKI 60 (10): 474 – 479.
Price A, Sylvia, Wilson M, Lorraine 2003. Patofisiologi, Edisi 6, Jakarta. Penerbit buku kedokteran ECG, p 1385-1389.
Raafat BM, Aziz SW, Latif NA, and Hanafi AM 2011. Human Telomerase Reverse Trancriptase (hTERT) Gene Expression in Rheumatoid Arthritis (RA) Patients after Usage of Low Level Laser Therapy (LLLT). Austr Journal of Applied Sci 5 (10): 1 – 8.
Rohmah W and Aswin S 2001. Tua dan Proses menua. Berkala ilmu Kedokteran 33 (4): 221-227.
Steer SE, Williams MK, Kato B et al 2007. Reduce Telomere Length in Rheumatoid Arthritis is Independent of Disease activity and duration. Ann Rheum Dis 66: 476 – 480. Doi: 10.1136/ard.2006.059188.
Schonland SO, Lopez C, Widmann T, Zimmer J, Bry E, Goronzy JJ, and Weyland CM 2003. Premature telomeric loss in Rheumatoid Arthritis is genetically determined and involves both myeloid and lymphoid cell lineages. PNAS 100 (23): 13471 - 13476.
Underwood JCE 2002. Patologi. Umum dan sistematik. Second Ed. Terjemahan Sarjadi. Penerbit EGC, Jakarta.
Vogts S, Iking-Konect T, Hug F, Andrassy K, Hansch GM 2003. Evidence for Replicative Senescence of T Cells derived from patients with Wegner’s Granulomatosis. Kidney Int 63 (6): 2144 - 2151.
Wardana M 2012. Psikoneuroimunologi di bidang Dermatologi. http://madewardhana.com/artikel/psikoneuroimunologi-di-bidang-dermatologi.html. Diakses pada tanggal 18/12-2012.
Weng NP 2006. Aging of Immune System: How Much Can the Adaptive Immune System Adapt? Immunity 24 (5): 495-499.
Weng NP 2008. Telomere and Adaptive Immunity. Mech Ageing Dev, doi:10.1016/j.mad.2007.11.005.
Weng NP 2012. Telomeres and Immune Competency. Current Opinion on Immunology 24 (Issue 4) : 470 – 475.
Widiani W, Nuhonni SA, Murdana IN, Sumariyono, Bardosono 2011. Efek Program Latihan Tangan di Rumah terhadap Deksteritas Bimanual Penderita Artritis Reumatoid. J Indon Med assoc 61 (11) : 435 -441.
Wu CH, Hsieh SC, Li KJ, Lu MC, and Yu CL 2007. Premature Telomere Shorthening in polymorphonuclear neutrophils from patients with systemic lupus erytematosus is related to the lupus disease activity. Lupus 16 : 265 - 272.
Zhou JG, Qing YF, Yang QB, Xie WG, and Zhao MC 2011. Changes in the expression of Telomere maintenance genes might play a role in the pathogenesis of systemic lupus erythematosus. Lupus 20 : 820 – 828.
